Sara Vaz-Pereira

Intravitreal aflibercept for choroidal neovascularisation in angioid streaks.

Choroidal neovascularisation (CNV) is a well-known complication of angioid streaks (AS). It affects 42–86% of patients and if untreated can result in significant vision loss.1 Treatment options have included laser photocoagulation and photodynamic therapy;1,2 with the advent of anti-vascular endothelial growth factor (VEGF) therapies, off-label anti-VEGF has become the treatment of choice and both bevacizumab and ranibizumab have been shown to be effective.1–3 We describe the off-label use of 2 mg intravitreal aflibercept in two patients as primary treatment for AS-associated CNV (AS-CNV).

Real-world outcomes of anti-VEGF treatment for retinal vein occlusion in Portugal.

Purpose Retinal vein occlusion (RVO) is an important cause of visual disability in the modern world. We aim to evaluate the real-world outcomes of patients with RVO treated with anti-vascular endothelial growth factor (VEGF) in Portugal. Methods We performed a retrospective, observational, multicenter study including 8 centers across Portugal and 200 patients treated with either ranibizumab or bevacizumab. Data were collected at 3 time points: time of diagnosis (0 time point) and 6 and 12 months after initiating treatment. Demographic and clinical data were collected. Results Median visual acuity (VA) and central macular thickness (CMT) improved in the branch RVO (BRVO), central RVO (CRVO), bevacizumab, and ranibizumab groups at 6 and 12 months compared to baseline, with CMT improving further only in the CRVO and ranibizumab groups between 6 and 12 months (p = 0.002 and p = 0.001, respectively). The CMT was lower in the ranibizumab group compared to the bevacizumab group both at 6 and 12 months (p<0.02). Median CMT improved in both the good and poor baseline VA groups at 6 and 12 months compared to baseline (p<0.001). Median VA only improved for the group with poor baseline VA at 6 and 12 months of follow-up (p<0.001). Regression analysis identified several baseline variables as predictors of visual outcomes at 6 and 12 months, with different results depending on the analyzed group. Conclusions Both treatments were effective, although less effective than results reported in clinical trials. The morphologic response was better with ranibizumab compared to bevacizumab, although functionally there were no differences.

Vascular endothelial growth factors and placenta growth factor in retinal vasculopathies: Current research and future perspectives

Vision loss due to disease or degeneration of the eye (retina, choroid, retinal veins, or macula) is a leading cause of blindness worldwide. In most cases, vision-threatening ocular diseases are accompanied by abnormal changes in the vasculature of the eye, especially the retina, and these conditions are collectively referred to as retinal vasculopathies. Impaired blood supply or hypoxia stimulates angiogenesis in the vascular and non-vascular sections of the eye, which results in neovascularization, leading to conditions such as diabetic retinopathy or age-related macular degeneration. Studies show that vascular endothelial growth factors: VEGF-A, VEGF-B, and placental growth factor (PlGF) are elevated in these diseases, and hence, these factors could be used as markers for disease prognosis and therapy. In this review, we discuss the function of these growth factors in normal development and disease, with focus on ocular disorders and emphasize the importance of accurately determining their levels in the vitreous and serum of patients for correct diagnosis and therapy.

Intrabursal and Subhyaloid Hemorrhages in Valsalva Retinopathy.

The vitreous cavity is a compartmentalized structure comprises vitreous gel containing the liquid-filled bursae, cisterns, lacunae, canals, and fissures. Optical coherence tomographic techniques have greatly aided our understanding of the complex spatial relationships between vitreous compartments. However, the boundaries to solute passage across the vitreous cortex and within the vitreous cavity have not been specifically studied. The central vitreous gel is predominantly acellular and highly hydrated (approximately 98% water). In Fig. 1. Intrabursal hemorrhage due to valsalva retinopathy. A 36-year-old man presented with sudden onset floaters in the left eye after heavy lifting. Ophthalmoscopy revealed a boatshaped hemorrhage with indistinct margins adjacent to the inferior vascular arcade and a second hemorrhage inferior to the optic disk (A). There was no leakage identified on fluorescein angiography, but blockage over the vein the hemorrhage likely originated from (B; red arrowhead). The vitreous was imaged using swept source optical coherence tomography (DRI OCT-1 Atlantis 3D; Topcon Medical Systems, Oakland, NJ), and the areas imaged with line scans are illustrated in the reflectance image (C). Note that erythrocytes are predominantly localized within the vitreous gel between the premacular bursa (stars) and the cortical vitreous. The bursal cavity itself is relatively devoid of erythrocytes; however, accumulation of erythrocytes within the vitreous adjacent to the bursa creates the impression that the bursal wall is lined with blood. Also note that the vitreous is attached at the macula, and the subhyaloid space is optically clear without any evidence of hemorrhage.

The Portuguese Experience with Ocriplasmin in Clinical Practice

Aim: Evaluate the real-life experience with ocriplasmin on vitreomacular traction (VMT) release and full-thickness macular hole (FTMH) closure in Portugal. Methods: Multicentric, retrospective study of 83 eyes of 78 patients who were treated with intravitreal ocriplasmin for VMT with and without FTMH. Primary outcomes were VMT release and FTMH closure. Secondary outcomes included visual acuity changes and structural features on spectral-domain ocular coherence tomography. Results: VMT resolved in 47 of the 83 eyes (56.6%) and 6 of the 12 FTMH were closed (50.0%). Mean best-corrected visual acuity (BCVA) improved from 65.1 at baseline to 70.8 ETDRS letters at the end of follow-up (p < 0.0001) with a mean follow-up of 138.8 days. Improvement in BCVA was significantly better in eyes with VMT release (p = 0.021). Approximately 73% of patients had normal ellipsoid zone integrity at the end of follow-up, 87% had no neurosensorial detachment and 40% had no intra- or subretinal fluid. Conclusion: VMT release and FTMH closure were achieved in more than half of the treated eyes and were correlated with significant BCVA improvements and favorable baseline characteristics. In fact, if a careful patient selection is carried out, VMT resolution with ocriplasmin can be optimized, tailoring the best approach to each patient.

Evaluation of the growth factors VEGF-a and VEGF-B in the vitreous and serum of patients with macular and retinal vascular diseases

Abstract VEGF-A and VEGF-B are proangiogenic and key regulating factors for blood vessel growth. This study aims to compare VEGF-A and VEGF-B levels in the serum and vitreous of patients with neovascular pathology versus non-neovascular pathology. Our findings showed vitreous VEGF-A and VEGF-B levels increased in patients with neovascular disease, with higher levels of VEGF-A compared to VEGF-B (p ≤ .05). In the diabetic retinopathy (DR) group, higher vitreous VEGF-A or VEGF-B were found in proliferative diabetic retinopathy (PDR) than in non-PDR. The strong correlation between VEGF-A and VEGF-B demonstrates a simultaneous pathological increase of cytokines (p < .001), suggesting besides VEGF-A, VEGF-B is another contributor to ocular pathologies involving angiogenesis. There was no correlation between vitreous and serum VEGF-A or VEGF-B; however, a correlation between vitreous (VEGF-A or VEGF-B) and macular volume (p < .05) in DR patients was found. Targeting VEGF-A and VEGF-B in macular and retinal vascular diseases, involving neovascularization, may improve treatment outcomes.

Multicolor imaging in the diagnosis and follow up of type 2 acute macular neuroretinopathy

PurposeTo study the usefulness of multicolor imaging (MC) photographs in addition to near infrared reflectance (NIR) and spectral domain optical coherence tomography (SD-OCT) in the detection and follow up of acute macular neuroretinopathy (AMN).Patients and methodsSix patients with a complaint of paracentral scotomas in at least one eye due to AMN were included. They underwent full ophthalmic examination and multimodal imaging including color fundus photographs, (SD-OCT), NIR, and MC at baseline and follow up.ResultsFour females and two males, aged 19–64 years, and eight eyes affected by AMN, were included. Acute phase SD-OCT in all patients confirmed the diagnosis of type 2 AMN with partial recovery of the outer retina in the convalescent phase. NIR and MC elicited in all cases hypo-reflective AMN lesions pointing toward the fovea. MC exhibited a higher contrast between the affected and the physiologic retina that slowly attenuated during the follow up showing a decrease in the hypo-reflectance of the lesions.ConclusionMC imaging was more detailed than fundus color photographs and as detailed as NIR in the detection of AMN. When available, MC imaging should complement SD-OCT and NIR in the diagnosis and follow up of this rare inflammatory condition that may be underdiagnosed.

Author's Reply to Comments to: Real-World Outcomes of Anti-VEGF Treatment for Retinal Vein Occlusion in Portugal

We appreciate the comments from Călugăru and Călugăru regarding our publication on real-world outcomes of antivascular endothelial growth factor treatment for retinal vein occlusion in Portugal (1) and acknowledge their enthusiasm in writing letters to the editor (2). We would like to address some of the authors’ concerns; however, because of article length limitations, we must be succinct. While randomized controlled trials (RCTs) are considered the gold standard to check the safety and efficacy of a drug, real-word studies are important to give real-life evidence as RCTs have precise eligibility criteria that may not represent routine clinical practice, where all patients need to be treated (3). We agree that some data are missing from the study; however, we performed a multicenter retrospective data collection, with the inherent limitations. We included data from patients with retinal vein occlusion, either central retinal vein or branch retinal vein occlusion, and though we agree that the evolution and prognosis differ, the baseline demographics and characteristics are clearly separated and demonstrated in Table I as well as the results regarding visual acuity (VA) and central macular thickness (1). Furthermore, while spectral-domain optical coherence tomography was used in all cases, a tomographic analysis was beyond our scope and some of the variables suggested were not considered significant to collect, such as subfoveal choroidal thickness. Indeed, our study is in line with landmark RCTs, which usually have as primary outcomes VA and central macular thickness improvements (3). Regarding frequency of treatment, we concede that the patients were undertreated and that is stated in the study (1). As discussed, real-world results may not mimic RCTs because of various reasons, including constraints of the public health care system and overbooked clinics, which may determine less intensive treatments. Examining real-word data is nevertheless important as it raises awareness and allows identification of areas to improve and implementation of strategies. On the topic of VA, our results showed that a worse VA at baseline was a predictor of a worse VA at 6 and 12 months (1). This is in accordance with previous studies that indicated that the VA at presentation has a major prognostic significance. Natural history studies on central retinal vein occlusion reported improvement in only 20% of eyes with vision between 20/50 and 20/200 and stabilization or worsening of vision in 80% of eyes with baseline vision worse than 20/200 (4). The comment by Călugăru and Călugăru is related to the visual gain and in that circumstance, as also discussed in our publication, patients with worse VA have a higher potential to recover than patients with good VA, as the latter have a smaller margin for improvement. Concerning the bibliography, the references used were appropriate and comprehensive (1). There are many interesting and meritorious articles and there is always need for a selection process. Finally, as Drs. Călugăru and Călugăru have valid opinions and have extensively commented on other articles regarding vein occlusion (2), we would be interested in reading a new publication by their group on the subject.

Acknowledgements to the Referees

www.karger.com/ore Abcouwer, Steven Ajtony, Csilla Aragona, Pasquale Arévalo, J. Fernando Arias, Lluis Augustin, Albert J. Aveleira, Célia A. Balaskas, Konstantinos Barsam, Allon Bi, Hongsheng Bowl, Wadim Bringmann, Andreas Chatziralli, Irini Chowers, Itay Christoforidis, John Costa, Esmeralda Cruchaga, Carlos Davis, Benjamin De Groef, Lies Digiuni, Maurizio Donate-Lopez, Juan Duran, Juan Fernandes, Rosa Fonollosa, Alex Georgiou, Anne Harrison, Ian He, Mingguang Heeren, Tjebo Hjortdal, Jesper Hussain, Ali Jaksic, Vesna Kalogeropoulos, Christos Kanonidou, Evgenia Kondo, Hiroyuki Kroupis, Christos Kühlewein, Laura Kusaka, Shunji Lai, Chi-Chun Lengyel, Imre Martin, Gottfried Martins, João Mathew, Raeba Medeiros, Marco D. Mesquida, Marina Murta, Joaquim Nakahara, Tsutomu Ni Dhubhghaill, Sorcha Noda, Kousuke Panos, Georgios Paques, Michel Parisi, Vincenzo Picaud, Serge A. Pinazo-Duran, Maria Dolores Porciatti, Vittorio Quadrado, Maria João Radach, Ralph Rezende, Flavio Rotenstreich, Ygal Rozema, Jos J. Santiago, Ana Raquel Sappington, Rebecca M. Saxena, Sandeep Schlottmann, Patricio Schmetterer, Leopold Sheha, Hosam Shieh, Chi-Chang Silva, Rufino Stahl, Andreas Stalmans, Peter Stieger, Knut Strong, Stacey Suzuma, Kiyoshi Terasaki, Hiroko Tian, Kailin Toth, Marta Tsubota, Kazuo Vujosevic, Stela Watson, Peter Xu, Heping Yanagi, Yasuo Yang, Sung Jae Zarogiannis, Sotirios